The semi-synthetic production of a 7-acylamidodesacetoxycephalosporin antibiotic from a penicillin starting material has been of exceptional importance since the advent of the invention of Morin and Jackson (U.S. Pat. No. 3,275,626) who describe and claim a process for converting a penicillin sulfoxide ester to a desacetoxycephalosporanic acid ester. Subsequently, improvements were made upon this Morin-Jackson process. Robin D. G. Cooper found that the use of certain tertiary carboxamide solvents (British Pat. No. 1,204,972) or certain tertiary sulfonamide solvents (British Pat. No. 1,204,394) directed the heat rearrangement of the penicillin sulfoxide esters more specifically toward production of the corresponding desacetoxycephalosporin esters and permitted the use of lower temperatures. Hatfield (U.S. Pat. No. 3,591,585) improved upon the Cooper contributions by finding that the conversion of a penicillin sulfoxide ester to a desacetoxycephalosporin ester by heating under acid conditions in the presence of a tertiary carboxamide solvent can be further improved by carrying out the reaction in the presence of both a sulfonic acid and means for removing or inactivating water present in the reaction mixture.
The mechanism which is postulated in U.S. Pat. No. 3,275,626 for the conversion of the penicillin sulfoxide ester to a desacetoxycephalosporanic acid ester is by formation of a sulfenic acid involving scission of the S-C.sub.2 bond. This mechanism has now been conclusively established, and it furthermore has been shown (R. D. G. Cooper, J.A.C.S, 92, (1970) pp. 5010-5011) that, under the conditions of reaction, a thermal equilibrium between the sulfoxide starting material and the sulfenic acid intermediate is established. One approach which would be advantageous in accomplishing the desired conversion of a penicillin sulfoxide or ester derivative thereof to its corresponding desacetoxycephalosporanic acid or ester derivative would be to trap the fleeting and unstable sulfenic acid intermediate in the form of a stable and isolatable intermediate. This intermediate could then be isolated and subsequently converted to the corresponding desacetoxycephalosporin or could be formed under conditions which, without isolation, would permit a virtual immediate conversion to the corresponding desacetoxycephalosporin.